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Updated: May 30, 2026
An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Interleukin-6 as a therapeutic target in human ovarian cancer
Jermaine Coward1, Hagen Kulbe, Probir Chakravarty
1Barts Cancer Institute, Queen Mary University of London, UK.
Purpose:
We investigated whether inhibition of interleukin 6 (IL-6) has therapeutic activity in ovarian cancer via abrogation of a tumor-promoting cytokine network.
Experimental Design:
We combined preclinical and in silico experiments with a phase 2 clinical trial of the anti-IL-6 antibody siltuximab in patients with platinum-resistant ovarian cancer.
Results:
Automated immunohistochemistry on tissue microarrays from 221 ovarian cancer cases showed that intensity of IL-6 staining in malignant cells significantly associated with poor prognosis. Treatment of ovarian cancer cells with siltuximab reduced constitutive cytokine and chemokine production and also inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer xenografts. In the clinical trial, the primary endpoint was response rate as assessed by combined RECIST and CA125 criteria. One patient of eighteen evaluable had a partial response, while seven others had periods of disease stabilization. In patients treated for 6 months, there was a significant decline in plasma levels of IL-6-regulated CCL2, CXCL12, and VEGF. Gene expression levels of factors that were reduced by siltuximab treatment in the patients significantly correlated with high IL-6 pathway gene expression and macrophage markers in microarray analyses of ovarian cancer biopsies.
Conclusion:
IL-6 stimulates inflammatory cytokine production, tumor angiogenesis, and the tumor macrophage infiltrate in ovarian cancer and these actions can be inhibited by a neutralizing anti-IL-6 antibody in preclinical and clinical studies.
Insights
Interleukin 6 (IL-6) drives ovarian cancer growth and inflammation. Inhibiting IL-6 with siltuximab shows therapeutic potential by reducing tumor progression and associated cytokines in preclinical and clinical settings.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interleukin 6 (IL-6) is a key cytokine implicated in cancer progression.
- IL-6 promotes tumor growth, angiogenesis, and immune suppression in various cancers.
- Understanding the role of IL-6 in ovarian cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the therapeutic activity of IL-6 inhibition in ovarian cancer.
- To determine if blocking IL-6 can abrogate a tumor-promoting cytokine network.
- To evaluate the efficacy of the anti-IL-6 antibody siltuximab in platinum-resistant ovarian cancer.
Main Methods:
- Combined preclinical xenograft models, in silico analysis, and a Phase 2 clinical trial.
- Immunohistochemistry to assess IL-6 staining in ovarian cancer tissues.
- Treatment with siltuximab in ovarian cancer cell lines and patient-derived xenografts.
- Clinical trial assessing response rate (RECIST and CA125) and plasma cytokine levels.
Main Results:
- High IL-6 staining in ovarian cancer cells correlated with poor prognosis.
- Siltuximab treatment reduced cytokine production, tumor growth, macrophage infiltration, and angiogenesis in preclinical models.
- In the clinical trial, one partial response and disease stabilization were observed in evaluable patients.
- Siltuximab treatment led to a significant decline in IL-6-regulated plasma markers (CCL2, CXCL12, VEGF).
Conclusions:
- IL-6 blockade with siltuximab demonstrates therapeutic potential in ovarian cancer.
- IL-6 inhibition can disrupt inflammatory cytokine production, angiogenesis, and macrophage infiltration.
- These findings support the targeting of IL-6 as a therapeutic strategy for ovarian cancer.
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